AB0417 JAK INHIBITORS AND LIVER INVOLVEMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS: RISK ASSESSMENT OF NAFLD AND SAFETY PROFILE IN HBV INFECTIONS
Authors: G. Busto, C. Rotondo, N. Maruotti, F. D’onofrio, A. Mele, F. P. Cantatore, A. Corrado
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Janus kinase inhibitors (JAK-i) are increasingly used in the treatment of Rheumatoid Arthritis (AR). Hypertransaminasemia is one of the described side effects of this class of drugs. <h3>Objectives</h3> The aim of the study is to evaluate the possible hepatotoxicity, the risk of NAFLD onset, and the reactivation of HBV and HCV in patients with AR and JAK-i therapy. <h3>Methods</h3> 78 patients with AR (81%F) were enrolled with an average disease duration of 15±7 years, BMI 26±4. The inclusion criteria were age &gt; 18 years, fulfillment of ACR/EULAR 2010 criteria for AR, and stable intake for at least 3 months of JAK-i in monotherapy or combined therapy with methotrexate (MTX) and/or steroid. <h3>Results</h3> The average therapy duration of JAK-i treatment (Baricitinib, Filgotinib, Tofacitinib or Upadacitinib) was of 67±50 weeks. 32% of patients were on combined therapy with MTX and 22% took steroids (mean dose in prednisone equivalents of 5.5±2.5 mg/day). No patients had positivity for HCV antibodies at the beginning of JAK-i therapy, and no one reported alcohol abuse. At the beginning of JAK-i therapy, 9% of patients had hepatic steatosis on abdominal ultrasound and 26% had occult HBV infection. 8% of patients had hypertransaminasemia before starting therapy with JAK-i. During treatment with JAK-i, hypertransaminasemia occurred in 6% of patients; of these 20% had already known hepatic steatosis, 40% were occult HBV carriers and 40% were with combined therapy with MTX. Particularly, hypertransaminasemia was detected in 8% of patients treated with Baricitinib and in 8% of patients with Tofacitinib. No patients treated with Filgotinib and Upadacitinib developed hypertransaminasemia during follow-up. JAK-i treatment was not stopped in any patient with hypertransaminasemia. 14% had NAFLD during treatment with JAK-i, and no patients had hepatic steatosis with hypertransaminasemia above 3 times normal values. Among patients who developed NAFLD after JAK-i treatment, 18% were overweight, 36% were obese, 27% were in therapy with steroids, and 18% were with combined therapy with MTX. NAFLD has been detected in 16% of patients treated with Baricitinib, 8% of patients treated with Tofacitinib, and 15% of patients treated with Upadacitinib, no patients treated with Filgotinib showed onset of NAFLD. Among patients with previous episodes of hypertransaminesia for other reasons, JAK-i treatment didn't cause alterations of bio-humoral indexes of hepatic function. No HBV reactivation occurred in patients with occult HBV infection during treatment with JAK-i. <h3>Conclusion</h3> JAK-i treatment in patients with occult HBV infection or previous NAFLD has a good safety profile. In terms of hypertransaminasemia with or without NAFLD, the risk of liver dysfunction appears to be very low during JAK-i treatment, both in monotherapy or in MTX combination treatment. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.